ABSTRACT
Principles of transfusion strategy have been used for neonates and children similar to adults. However, due to substantial discrepancies between physiology/pathology in children and in their adult counterparts, decisions, indications, and doses are different from those of adults, especially in neonates. Specific data and practice guidelines for blood product transfusion are reported owing to the experience of pediatrics and neonatology units and partners of the French Blood product bank.
Subject(s)
Blood Transfusion/standards , Neonatology , Pediatrics , Practice Guidelines as Topic , Blood Component Transfusion/standards , Blood Grouping and Crossmatching , Blood Transfusion/legislation & jurisprudence , Blood Transfusion/methods , Child , Child, Preschool , France , Humans , Infant , Infant, Newborn , Parental Consent/legislation & jurisprudence , Transfusion Reaction/prevention & controlABSTRACT
Data on post-transplant iron overload (IO) are scarce in pediatrics. We conducted a prospective multicenter cohort study (Leucémie de l'Enfant et de l'Adolescent cohort) to determine the prevalence and risk factors of IO in 384 acute leukemia survivors transplanted during childhood. Prevalence of IO (ferritin level ⩾350 ng/mL) was 42.2% (95%CI 37.2-47.2%). Factors significantly associated with IO were: 1) in univariate analysis: older age at transplant (P<0.001), allogeneic versus autologous transplantation (P<0.001), radiation-based preparative regimen (P=0.035) and recent period of transplantation (P<0.001); 2) in multivariate analysis: older age at transplant in quartiles (Odds Ratio (OR)=7.64, 95% CI: 3.73-15.64 for age >12.7 years and OR=5.36, 95% CI: 2.63-10.95 for age from 8.2 to 12.7 years compared to age < 4.7 years), acute myeloid leukemia (OR=3.23, 95% CI: 1.47-7.13), allogeneic graft (OR=4.34, 95% CI: 2.07-9.12 for alternative donors and OR=2.53, 95% CI: 1.2-5.33 for siblings, compared to autologous graft) and radiation-based conditioning regimen (OR=2.45, 95% CI: 1.09-5.53). Graft-versus-host disease was an additional risk factor for allogeneic graft recipients. In conclusion, IO is a frequent complication in pediatric long-term survivors after transplantation for acute leukemia, more frequently observed in older children, those transplanted from alternative donors or with graft-versus-host disease.
Subject(s)
Cancer Survivors , Ferritins/blood , Hematopoietic Stem Cell Transplantation , Iron Overload/blood , Iron Overload/epidemiology , Leukemia, Myeloid, Acute/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Transplantation Conditioning , Age Factors , Allografts , Child , Female , Graft vs Host Disease/blood , Graft vs Host Disease/epidemiology , Humans , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/epidemiology , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Prevalence , Risk Factors , Tissue DonorsABSTRACT
INTRODUCTION: According to the European Society of Pediatric Oncology (SIOPE) standard of care guidelines, high-quality care of children and adolescents with cancer needs to be delivered by well-trained multidisciplinary teams in specialist centers working with designated shared-care local centers in a so-called hub-and-spoke model. The Diplôme Inter-Universitaire d'Oncologie Pédiatrique (DIUOP) is the only European training program in pediatric oncology in French for all physicians involved in care of patients with pediatric malignancies. In agreement with the SIOPE syllabus, the DIUOP is composed of training courses (120h), on-site practical training in a specialist center, and a research project to be defended before an examining board. METHOD: All graduates received a questionnaire to describe their current professional position. A comprehensive PubMed analysis retrieved all papers published form DIUOP research projects. RESULTS: From 2000 to 2011, 290 physicians were trained: 242 pediatricians, 21 surgeons, and 19 radiation therapists. Eight had another specialty including imaging, hematology, and pathology. Ninety-two were initially trained outside of France: 50% in Europe (mainly in Italy, Belgium, and Switzerland), 42% in Africa and the Middle East, and 8% in South America. Of the 266 graduates, 74% answered the questionnaire, and 90% of them take care of children and adolescents with cancer. Sixty-nine articles, i.e., one out of four research projects, were published in 34 journals with a median impact factor of 3.5 (0-22.6), 85% in English. CONCLUSION: DIUOP is the only French-speaking European education program providing a high-quality, professionalizing, and comprehensive multidisciplinary training program for French and international specialists taking care of children and adolescents with cancer.
Subject(s)
Hematology/education , Medical Oncology/education , Pediatrics/education , Adolescent , Child , France , Humans , Interdisciplinary Communication , Neoplasms/therapy , Surveys and QuestionnairesABSTRACT
BACKGROUND AND PURPOSE: Brain tumours are the most frequent solid tumours in children and the most frequent radiotherapy indications in paediatrics, with frequent late effects: cognitive, osseous, visual, auditory and hormonal. A better protection of healthy tissues by improved beam ballistics, with particle therapy, is expected to decrease significantly late effects without decreasing local control and survival. This article reviews the scientific literature to advocate indications of protontherapy and carbon ion therapy for childhood central nervous system cancer, and estimate the expected therapeutic benefits. MATERIALS AND METHODS: A systematic review was performed on paediatric brain tumour treatments using Medline (from 1966 to March of 2014). To be included, clinical trials had to meet the following criteria: age of patients 18 years or younger, treated with radiation, and report of survival. Studies were also selected according to the evidence level. A secondary search of cited references found other studies about cognitive functions, quality of life, the comparison of photon and proton dosimetry showing potential dose escalation and/or sparing of organs at risk with protontherapy; and studies on dosimetric and technical issues related to protontherapy. RESULTS: A total of 7051 primary references published were retrieved, among which 40 clinical studies and 60 papers about quality of life, dose distribution and dosimetry were analysed, as well as the ongoing clinical trials. These papers have been summarized and reported in a specific document made available to the participants of a final 1-day workshop. Tumours of the meningeal envelop and bony cranial structures were excluded from the analysis. Protontherapy allows outstanding ballistics to target the tumour area, while substantially decreasing radiation dose to the normal tissues. There are many indications of protontherapy for paediatric brain tumours in curative intent, either for localized treatment of ependymomas, germ-cell tumours, craniopharyngiomas, low-grade gliomas; or panventricular irradiation of pure non-secreting germinoma; or craniospinal irradiation of medulloblastomas and metastatic pure germinomas. Carbon ion therapy is just emerging and may be studied for highly aggressive and radioresistant tumours, as an initial treatment for diffuse brainstem gliomas, and for relapse of high-grade gliomas. CONCLUSION: Both protontherapy and carbon ion therapy are promising for paediatric brain tumours. The benefit of decreasing late effects without altering survival has been described for most paediatric brain tumours with protontherapy and is currently assessed in ongoing clinical trials with up-to-date proton devices. Unfortunately, in 2015, only a minority of paediatric patients in France can receive protontherapy due to the lack of equipment.
Subject(s)
Brain Neoplasms/radiotherapy , Child , Forecasting , Heavy Ion Radiotherapy , Humans , Practice Guidelines as Topic , Proton TherapyABSTRACT
We report French prospective experience with reduced-intensity conditioning-allo-SCT in 46 patients (median age: 15.5 years, 4.8-20.2) presenting high-risk AL (n=11), Hodgkin's lymphoma (n=15) or solid tumors (n=20). Graft sources were BM (n=21), PBSC (n=20) and cord blood (CB; n=5) from related (n=20) or unrelated (n=26) donors. For CB grafts, only one patient out of five achieved sustained engraftment. For PBSC/BM grafts, engraftment rate was 95%, hematopoietic recovery times were not significantly different between BM, PBSC, sibling or unrelated grafts, day+100. Full donor chimerism was achieved in 94% of patients, and incidences of primary acute GVHD and chronic GVHD were 49% and 14%, respectively. Underlying disease was fatal in 39% of patients. TRM was 6.9%. Three-year OS was 49.15%. OS and EFS were not significantly different between patients transplanted with different grafts and with or without primary GVHD. Patients with solid tumor or measurable disease at transplant had poorer outcomes. Three-year EFS: 33.3% for ALL, 75.0% for AML, 51.8% for Hodgkin's lymphoma, 28.6% for neuroblastoma and 22.2% for sarcoma patients. This multicentre study concluded that Bu/fludarabine/anti-thymocyte globulin conditioning with PB or BM, related or unrelated grafts in patients with various malignancies at high-risk for transplantation toxicity results in high engraftment rates, low TRM and acceptable survival.
Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Neoplasms/therapy , Transplantation Conditioning/methods , Adolescent , Adult , Child , Child, Preschool , Female , France , Humans , Male , Neoplasms/surgery , Prospective Studies , Tissue Donors , Transplantation, Homologous , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Autoimmune hemolytic anemia is a rare condition in children. Little is known about its initial presentation and the subsequent progression of the disease. DESIGN AND METHODS: Since 2004, a national observational study has been aiming to thoroughly describe cases and identify prognostic factors. Patients from all French hematologic pediatric units have been included if they had a hemoglobin concentration less than 11 g/dL, a positive direct antiglobulin test and hemolysis. Evans' syndrome was defined by the association of autoimmune hemolytic anemia and immunological thrombocytopenic purpura. Data from patients' medical records were registered from birth to last follow-up. Autoimmune hemolytic anemia was classified as primary or secondary. Remission criteria, qualifying the status of anemia at last follow-up, were used with the aim of identifying a subgroup with a favorable prognosis in continuous complete remission. RESULTS: The first 265 patients had a median age of 3.8 years at diagnosis. In 74% of cases the direct antiglobulin test was IgG/IgG+C3d. Consanguinity was reported in 8% of cases and first degree familial immunological diseases in 15% of cases. Evans' syndrome was diagnosed in 37% of cases. Autoimmune hemolytic anemia was post-infectious in 10%, immunological in 53% and primary in 37% of cases. After a median follow-up of 3 years, 4% of children had died, 28% were still treatment-dependent and 39% were in continuous complete remission. In multivariate analysis, IgG and IgG+C3d direct antiglobulin tests were associated with a lower rate of survival with continuous complete remission (adjusted hazard ratio, 0.43; 95% confidence interval, 0.21-0.86). CONCLUSIONS: This nationwide French cohort is the largest reported study of childhood autoimmune hemolytic anemia. The rarity of this condition is confirmed. Subgroups with genetic predisposition and underlying immune disorders were identified.
Subject(s)
Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/therapy , Adolescent , Anemia, Hemolytic, Autoimmune/epidemiology , Child , Child, Preschool , Female , France/epidemiology , Health Surveys/statistics & numerical data , Humans , Infant , Infant, Newborn , Male , Multivariate Analysis , Outcome Assessment, Health Care/statistics & numerical data , Prognosis , Registries/statistics & numerical dataABSTRACT
BACKGROUND: The association between acute childhood leukaemia and residing next to petrol stations and automotive repair garages was analysed in a national registry-based case-control study carried out in France in 2003-2004. METHODS: Population controls were frequency matched with cases on age and gender. Data were collected by standardised telephone interview with the mothers. The latter were asked to report the proximity of their homes to petrol stations, automotive repair garages and other businesses from the conception of the index child to the diagnosis (for cases) or interview (for controls). Odds ratios were estimated using unconditional regression models adjusted for age, gender, number of children under 15 years of age in the household, degree of urbanisation and type of housing. RESULTS: 765 cases of acute leukaemia and 1681 controls were included. Acute leukaemia was significantly associated with residence next to petrol stations or automotive repair garages (OR 1.6, 95% CI 1.2 to 2.2) and next to a petrol station (OR 1.9, 95% CI 1.2 to 3.0). The OR showed no tendency to increase with duration of exposure. The results were not modified by adjustment for potential confounding factors including urban/rural status and type of housing. CONCLUSIONS: The results support the findings of our previous study and suggest that living next to a petrol station may be associated with acute childhood leukaemia. The results also suggest that the role of low-level exposure to benzene in acute childhood leukaemia deserves further evaluation.
Subject(s)
Environmental Exposure/adverse effects , Gasoline/adverse effects , Leukemia/epidemiology , Acute Disease , Adolescent , Age Distribution , Air Pollutants/adverse effects , Benzene/adverse effects , Carcinogens, Environmental/adverse effects , Case-Control Studies , Child , Child, Preschool , Educational Status , Environmental Exposure/analysis , Environmental Monitoring/methods , Epidemiological Monitoring , Female , France/epidemiology , Humans , Infant , Infant, Newborn , Leukemia/etiology , Male , Residence Characteristics , Sex Distribution , Social ClassABSTRACT
The authors report 2 cases of neuroblastoma-associated hepatomegaly, which were treated using a Silastic patch, and discuss in the light of recent reports, the technical aspects and outcome of these children. They were satisfied by the decompression achieved with the patch and believe there is no increased risk in using Silastic rather than other types of material. The outcome for these children depends more on the evolution of the underlying disease than the technical aspects of the abdominal decompression.
Subject(s)
Decompression, Surgical , Hepatomegaly/surgery , Liver Neoplasms/pathology , Neuroblastoma/pathology , Neuroblastoma/secondary , Combined Modality Therapy , Female , Hepatomegaly/etiology , Humans , Infant , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Male , Neuroblastoma/therapy , Treatment OutcomeABSTRACT
The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)+/-high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.
Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Brain Diseases, Metabolic/chemically induced , Methotrexate/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Age Factors , Brain Diseases, Metabolic/epidemiology , Brain Diseases, Metabolic/prevention & control , Child , Child, Preschool , Combined Modality Therapy , Dose-Response Relationship, Drug , Female , Humans , Infant , Male , Neurotoxins , Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy , Risk AssessmentSubject(s)
Anemia, Hemolytic, Autoimmune/epidemiology , Acute Disease , Adolescent , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/etiology , Anemia, Hemolytic, Autoimmune/therapy , Child , Child, Preschool , Chronic Disease , Cohort Studies , Cross-Sectional Studies , Diagnosis, Differential , Female , France/epidemiology , Humans , Infant , Male , Patient Care Team , Prognosis , Prospective Studies , Survival RateSubject(s)
Anemia, Hemolytic, Autoimmune/therapy , Acute Disease , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/etiology , Anemia, Hemolytic, Autoimmune/mortality , Autoantibodies/blood , Blood Group Incompatibility/blood , Blood Group Incompatibility/prevention & control , Child , Contraindications , Cryoglobulins/immunology , Diagnosis, Differential , Drug Administration Schedule , Erythrocyte Transfusion , Fluid Therapy , Follow-Up Studies , Humans , Immunization, Passive , Immunoglobulin G/blood , Isoantibodies/blood , Methylprednisolone/administration & dosage , Oxygen Inhalation Therapy , Plasma Exchange , Prednisolone/administration & dosage , Survival RateABSTRACT
The aim of this study was to assess the efficacy and adverse effects of 2-chlorodeoxyadenosine (2-CdA) and cytosine arabinoside (Ara-C) in children with refractory Langerhans cell histiocytosis (LCH) and haematopoietic dysfunction. Ten patients, with a median age at diagnosis of 0.5 years, were enrolled in this study. Treatment comprised at least two courses of Ara-C (1000 mg/m(2)/d) and 2-CdA (9 mg/m(2)/d) administered for 5d every 4 weeks; subsequent median follow-up was 2.8 years (range 0.03-6.4 years). Among the 7 patients who received at least two courses of therapy, disease activity decreased in 6 patients, and control of disease was achieved in all patients after a median delay of 5.5 months. All patients suffered World Health Organisation (WHO) grade 4 haematological toxicity. Two septic deaths occurred shortly after administration of the first course of 2-CdA/Ara-C; a third patient was withdrawn from the trial after the first course and subsequently died following haematopoietic stem cell transplantation. This series is small, but we conclude that 2-CdA and Ara-C combined chemotherapy probably has major activity in childhood refractory Langerhans cell histiocytosis.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematologic Diseases/complications , Histiocytosis, Langerhans-Cell/drug therapy , Chronic Disease , Cladribine/administration & dosage , Cytarabine/administration & dosage , Drug Therapy, Combination , Female , Humans , Infant , Infusions, Intravenous , Male , Pilot Projects , Survival AnalysisABSTRACT
UNLABELLED: Evans' Syndrome (ES) is defined as the combination of immune thrombocytopenia (ITP) and autoimmune haemolytic anemia (AIHA), in the absence of any known underlying etiology. Pathophysiology, epidemiology and outcome remain unclear. POPULATION: Thirty-six children (20 male, 16 female), who were diagnosed in the SHIP french centres (Société d'hématologie et d'immunologie pédiatrique) between 1990 and 2002 with ES, were included in this retrospective study. RESULTS: Median age at diagnosis was 4 years. In 21 children, ES occurred in the setting of consanguinity, family history of autoimmune/inflammatory disease, associated autoimmune disorder or immunoregulatory abnormalities (serum imunoglobulins, peripheral blood lymphocytes subsets, low level of the C3-C4 complement components, nuclear antibodies). Several successive treatments were used in this serie (median: 3, range: 0-10) including corticosteroid therapy (35/36), intravenous immunoglobulins (32/36), immunosuppressive agents (14/36), splenectomy (9/36) and anti CD 20 monoclonal antibodies (6/36). Patients with a low level of serum immunoglobulins were more often non-responders to corticosteroidtherapy/intravenous immunoglobulins and required more frequently further therapy (P=0.03). Three patients died (intracranial bleeding, N=2, Guillain-Barre syndrome; N=1). CONCLUSION: ES was a severe, life-threatening disease, requiring aggressive immunosuppressive therapy in as many as half the patients. Our forthcoming study aims to (i) describe homogeneously-studied and prospectively-analysed cohort of childhood ES, (ii) separate ES from specific immune deficiency (especially fas gene mutations), generalised autoimmune/inflammatory disorders and genetic diseases, (iii) identify well-defined ES subsets, (iv) establish prognostic factors and optimal treatment within these subsets.
Subject(s)
Anemia, Hemolytic, Autoimmune/pathology , Purpura, Thrombocytopenic, Idiopathic/pathology , Adolescent , Adrenal Cortex Hormones/therapeutic use , Age of Onset , Anemia, Hemolytic, Autoimmune/drug therapy , Anemia, Hemolytic, Autoimmune/genetics , Anemia, Hemolytic, Autoimmune/immunology , Child , Child, Preschool , Cohort Studies , Consanguinity , Female , France , Humans , Immunoglobulins, Intravenous/therapeutic use , Infant , Male , Prognosis , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/genetics , Purpura, Thrombocytopenic, Idiopathic/immunology , Retrospective Studies , Severity of Illness Index , SyndromeABSTRACT
From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucémie Aiguë Myéloblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 60+/-4 and 48+/-4%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 52+/-4% for non-allografted patients and 57+/-7% for allografted patients (P=NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MT-) than in patients randomized for MT (77.6+/-8 vs 59+/-8%; P=0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Protocols/standards , Leukemia, Myeloid, Acute/therapy , Adolescent , Bone Marrow Transplantation , Child , Child, Preschool , Dose-Response Relationship, Drug , Follow-Up Studies , France , Humans , Infant , Infant, Newborn , Leukemia, Myeloid, Acute/mortality , Remission Induction , Risk Assessment , Survival Analysis , Treatment OutcomeABSTRACT
The purpose of this study was to identify risk factors for hypothyroidism after bone marrow transplantation (BMT) for high-risk or relapsed acute lymphoblastic leukaemia (ALL) in children. In all, 388 children with acute lymphoblastic leukaemia underwent allogeneic bone marrow transplantation between 1984 and 1994. Overall 5-year survival was 54.6%. Thyroid function was assessed in the 153 patients with more than 5 years of follow-up. In total, 16 patients developed uncompensated hypothyroidism (UH) and 46 compensated hypothyroidism (CH) a median of 2.9 and 2.7 years, respectively, after BMT. Thyroid dysfunction-free survival rates were 73.2% after 5 years and 59.2% after 10 years. Three factors were significantly associated with the onset of hypothyroidism, namely age, bone marrow transplantation in second remission, and single-dose total body irradiation (TBI). Ultrasonography of the thyroid showed nodules in 10 of 35 patients. The median time from BMT to nodule detection was 7.8 years. Cytology (n=5) and surgery (n=4) showed no evidence of thyroid cancer. Four of the 14 patients who received cytoreduction without TBI but with busulphan and cyclophosphamide developed UH (n=2) or CH (n=2). We concluded that children who undergo BMT for ALL are at a high risk of subsequent thyroid dysfunction.
Subject(s)
Bone Marrow Transplantation/adverse effects , Hypothyroidism/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Risk Factors , Survivors , Transplantation, Homologous , Whole-Body Irradiation/adverse effectsABSTRACT
UNLABELLED: Neuroblastoma is the most frequent tumor observed in the newborn. The aim of this study was to review clinical features, treatment and outcome of newborns diagnosed with a localized neuroblastoma. POPULATION AND METHODS: Data from 52 cases treated according to the NBL 90 and 94 protocols between 1990 and 1999 in 18 French centers of pediatric oncology were analyzed. RESULTS: The median age at diagnosis was 12 days (range 0-28) with antenatal detection in 14 patients (27%). Tumor location was abdominal in 40 patients (adrenal in 20 of the 40), thoracic in eight, pelvic in three, and cervical in one. N-myc amplification was observed in one out of 40 evaluable cases. The size of the primary tumor was less than 5 cm in 25 cases, between 5 and 10 cm in 25 and more than 10 cm in two. Dumbbell tumor was observed in seven, of whom five had neurological deficit. One child died from hemorrhage after fine needle biopsy during diagnostic procedure. Primary surgical resection was attempted in 37 infants, of whom two died of surgery related complications and three had nephrectomy. Tumor was deemed as unresectable in 14 patients, and primary chemotherapy was given followed by surgical excision in 12. One of them died a few days after the beginning of chemotherapy. As a whole, continuous complete remission was achieved in 48 children, four of them after relapse. Overall survival was 92% with a median follow-up of 46 months (0-113 months). CONCLUSION: The excellent prognosis of localized NB in neonates needs very restrictive surgical indications, with well-established anatomic and imaging criteria. Indeed, chemotherapy based on weight and managed by expert teams should allow to perform surgical excision in safer conditions for unresectable tumors.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neuroblastoma/drug therapy , Neuroblastoma/surgery , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases , Male , Neuroblastoma/pathology , Prognosis , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
Neuroblastoma and its benign counterpart, ganglioneuroma, are pediatric neuroblastic tumors arising in the sympathetic nervous system from neural-crest cells. Neuroblastoma, the most common extra-cranial solid tumour during childhood, is unique for its broad spectrum of clinical virulence from spontaneous remission to rapid and fatal progression despite intensive multimodality therapy. To a large extent, outcome could be predicted by the stage of disease and the age at diagnosis. However, a number of molecular events in neuroblastoma tumors, accounting for the variability of outcome and response to therapy, have been identified over the past decades. Among these, MYCN amplification is the most relevant prognostic factor and was the first genetic marker, in paediatric oncology, to be included in clinical strategies as a guide for therapeutic decision. This has allowed the most suitable intensity of therapy to be delivered according to a risk-stratified strategy, from observation to megadose chemotherapy with stem cell transplantation. Recent advances in understanding the biology and genetics of neuroblastoma will ultimately allow to select poor-risk patients for appropriate future biologically based therapies.
Subject(s)
Genetic Markers , Neoplasm Staging , Neuroblastoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Neuroblastoma/genetics , Neuroblastoma/therapy , Patient Selection , Prognosis , Risk Factors , Stem Cell TransplantationSubject(s)
Leukemia, Myeloid, Acute/etiology , Neoplasms, Second Primary/etiology , Neutropenia/congenital , Neutropenia/genetics , Point Mutation , Receptors, Granulocyte Colony-Stimulating Factor/genetics , Cell Transformation, Neoplastic , Female , France , Humans , Infant , Male , Mass Screening , Neutropenia/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , RegistriesABSTRACT
PURPOSE: To determine whether, after very intensive induction and consolidation therapy in childhood AML, further maintenance therapy (MT) confers any advantage. PATIENTS AND METHODS: Three hundred-nine children with previously untreated AML were registered in the LAME 89/91 protocol. This three-cycle intensive regimen included an induction phase (mitoxantrone plus cytarabine) and, for non-allografted patients, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine. In the LAME 89 study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to be given or not MT after consolidation therapy. RESULTS: Out of 309 patients, 276 (90%) achieved a complete remission. The overall survival (OS) and event-free survival at 6 years for all patients were 60% +/- 6% and 48% +/- 6%, respectively. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no further treatment than in patients randomized for MT (81% +/- 13% vs 58% +/- 15%; p = 0.04) whilst the 5-year disease-free survival was not significantly different (60% +/- 19% vs 50% +/- 15%; p = 0.25). The improvement of OS in MT-patients appeared to be related to a higher salvage rate after relapse. CONCLUSION: Over 50% of patients can be cured of AML in childhood. In the context of a very short and drug-intensive regimen, low-dose MT, owing to the lack of improvement in disease control and the worsening of survival, should not be recommended. Over the past 20 years, the outcome of acute myeloid leukemia (AML) in children has improved substantially. In the eighties, complete remission (CR) was achieved in nearly 90% of patients but event-free survival (EFS) was poor. Myeloablative therapy followed by allogenic bone-marrow transplantation (allo BMT) from an HLA-identical sibling was demonstrated, in our experience, to be the treatment of choice for improving DFS in children with AML in first remission. The major issue was how best to maintain complete remission for patients without an HLA sibling donor. Whereas several groups continued to include low-dose MT and others decided to omit it, in 1991, our group undertook a prospective randomized trial (LAME 91 protocol), the main aim of which was to assess the efficacy of MT in addition to an intensive induction and consolidation chemotherapy. The main results have been published previously and are now updated and described in a higher number of patients.